WO2012029898A1 - Mitigating agent for alcohol-induced problems - Google Patents
Mitigating agent for alcohol-induced problems Download PDFInfo
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- WO2012029898A1 WO2012029898A1 PCT/JP2011/069876 JP2011069876W WO2012029898A1 WO 2012029898 A1 WO2012029898 A1 WO 2012029898A1 JP 2011069876 W JP2011069876 W JP 2011069876W WO 2012029898 A1 WO2012029898 A1 WO 2012029898A1
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- krill oil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/612—Crustaceans, e.g. crabs, lobsters, shrimps, krill or crayfish; Barnacles
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to an agent for alleviating damage to liver, blood, blood sugar and the like, and an alcohol metabolism promoter, in addition to disorders caused by alcohol intake, hangover, hangover and the like.
- Alcoholic drinks such as beer, wine, whiskey, sake and shochu have long been popular with people.
- various alcoholic beverages have been manufactured and sold so far, contributing to the rich diet of people.
- alcoholic beverages have an aspect of entertaining people, they may cause undesirable symptoms.
- Excessive drinking can cause hangover or hangover, and symptoms of drunkness (eg, headache, dizziness, nausea, dehydration) may not subside even after the next day of drinking.
- gout, liver dysfunction, etc. may develop due to excessive drinking for a long time. Symptoms caused by such alcohol are common in that they are caused by an increase in blood alcohol concentration caused by drinking.
- JP-A-11-276116 describes an alcohol metabolism promoter containing a processed pork product prepared from protease-treated pork (Patent Document 1).
- Patent Document 1 Japanese Patent Laid-Open No. 2002-161045 describes an alcohol metabolism improver containing a rice bran / soybean fermented extract (Patent Document 2).
- Patent Document 3 Japanese Patent Application Laid-Open No. 2001-226277 describes an alcohol absorption metabolism regulator containing processed soybean as an active ingredient (Patent Document 3).
- the present invention relates to a safe ingredient and a preparation, supplement, food, etc., containing a safe ingredient and an easy-to-ingest form that alleviates damage to the liver, blood, blood sugar, etc. in addition to sickness, hangover caused by alcohol consumption, etc.
- An object is to provide an alcohol metabolism promoter.
- krill oil has an unexpected effect on alcohol metabolism and completed the present invention.
- the present invention provides (11) to (16) an alcohol metabolism promoter, although not limited thereto.
- (11) An alcohol metabolism promoter containing krill oil.
- (12) The alcohol metabolism promoter according to (11), wherein krill oil is extracted from a krill-derived raw material with an organic solvent.
- (13) The alcohol metabolism promoter according to (11) or (12), wherein krill oil is extracted from ethanol from a krill-derived raw material.
- the present invention provides the following method.
- a method for promoting alcohol metabolism comprising administering an alcohol metabolism promoter containing krill oil.
- a method for preventing or ameliorating a disease caused by alcoholic liver disorder, tissue disorder associated with dehydration, or an increase in blood glucose level comprising administering an alcohol metabolism promoter containing krill oil.
- FIG. 3 is a diagram showing a test substance and alcohol administration schedule in Example 1. Rats were used as experimental animals and a 60% (v / v) ethanol solution was administered as alcohol. It is a figure which shows the change of the blood ethanol concentration of the rat in Example 2.
- the values in the figure represent average values.
- & is P ⁇ 0.05; vs untreated group (Student-t test), && is P ⁇ 0.01; vs untreated group (Student-t test), ** is P ⁇ 0.01; vs ethanol + olive oil group (Aspin-Welch test), and ## represents P ⁇ 0.01; vs ethanol + olive oil group (Student-t test).
- AST rat aspartate aminotransferase
- This enzyme activity is contained in the liver, and the ALT activity in blood is an indicator of liver damage.
- the values in the figure represent average values.
- $ represents P ⁇ 0.05; vs untreated group (Asp in-Welch test), and # represents P ⁇ 0.05; vs ethanol + olive oil group (Student-t test). It is a figure which shows the change of the blood glucose level (blood glucose level) of the rat in Example 2.
- FIG. From the left of the bar graph, untreated (A1), 60% (v / v) ethanol + olive oil (A2), 60% (v / v) ethanol + krill oil 200 mg / kg (A3), 60% (v / v) Ethanol + krill oil 1,000 mg / kg (A4).
- the values in the figure represent average values.
- $$ is P ⁇ 0.01; vs untreated group (Asp in-Welch test), ** is P ⁇ 0.01; vs ethanol + olive oil group (Aspin-Welch test), and # is P ⁇ 0.05; vs ethanol + olive oil group (Student-t test).
- FIG. The horizontal axis indicates the time (min) after alcohol intake.
- ⁇ Krill oil intake, ⁇ olive oil intake.
- the values in the figure represent the mean value (Mean ⁇ SE) of the ethanol concentration in exhaled breath collected from 5 subjects.
- FIG. The horizontal axis indicates the time (min) after alcohol intake.
- Solid line krill oil intake, dotted line: olive oil intake.
- Example 6 is a view showing a change with time of the acetaldehyde concentration in exhaled breath of Example 4 together with the result of Example 3.
- the horizontal axis indicates the time (min) after alcohol intake.
- ⁇ Krill oil intake
- ⁇ Olive oil intake
- ⁇ Purified fish oil intake
- ⁇ Soy lecithin intake.
- the krill may be any arthropod belonging to the arthropods Crustacea soft shell subclass, and the arthropods belonging to the order of the arthropod gate crustacea soft shell subclass Hon shrimp It includes arthropods belonging to the order of Euphausia superba, arthropods, crustaceans, crustaceans, submarine fowls, and for example, mysids caught in the sea near Japan.
- krill oil is oil obtained from the above krill.
- ⁇ Krill oil is characterized by a high phospholipid content.
- a phospholipid is known as a main component constituting a cell membrane, and has a hydrophilic phosphoric acid part and a hydrophobic fatty acid part.
- Phospholipids are divided into glycerophospholipids and sphingophospholipids depending on the skeleton.
- the phospholipids referred to in the present specification include all of them, but glycerophospholipids are preferable.
- glycerophospholipid examples include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, cardiolipin, and phosphatidic acid, and one or a mixture of two or more thereof.
- phosphatidylcholine is contained as at least phospholipid.
- the phospholipid content of krill oil is, for example, 5 to 80% by weight, particularly preferably 30 to 60% by weight.
- the krill oil can contain preferably 25% by weight or more, more preferably 35% by weight or more of phospholipid.
- the characteristic of krill oil is that it further contains ⁇ 3 highly unsaturated fatty acid.
- the ⁇ 3 highly unsaturated fatty acid is a fatty acid having 18 or more carbon atoms and 3 or more double bonds, preferably 5 or more carbon atoms, counted from the terminal carbon opposite to the carboxyl side of the fatty acid molecule. It means a fatty acid in which the third and fourth carbons are bonded by a double bond.
- Examples of such fatty acids include ⁇ -linolenic acid (18: 3), eicosapentaenoic acid (20: 5), docosapentaenoic acid (22: 5), docosahexaenoic acid (22: 6), and the like.
- the ⁇ 3 highly unsaturated fatty acid may exist in a free state or may exist in a lipid state via an ester bond.
- the proportion of the ⁇ 3 highly unsaturated fatty acid in the total fatty acids present in krill oil is, for example, 5 to 60% by weight, preferably 10 to 50% by weight or more, and more preferably 10 to 30% by weight. For the purposes of the present invention, it is preferably 5% by weight or more, more preferably 10% by weight or more, and still more preferably 15% by weight or more.
- those containing eicosapentaenoic acid in an amount of 2% by weight or more, preferably 10% by weight or more and / or docosahexaenoic acid in an amount of 1% by weight or more, preferably 3% by weight or more are preferred.
- the krill oil may further contain astaxanthin.
- Astaxanthin is a compound belonging to carotenoids commonly found in crustaceans such as crabs and shrimps. Astaxanthin may exist in a free state or in the form of a lipid via an ester bond, for example, 20 to 1,000 ppm, preferably 50 to 600 ppm, more preferably 50 to 500 ppm, and still more preferably Is contained in krill oil at 100 to 400 ppm, particularly preferably 100 to 250 ppm.
- the krill oil used in the present invention may be produced by any method as long as it has the above-mentioned characteristics.
- the krill oil can be produced by referring to known methods described in WO2010 / 035749A1, WO2010 / 035750A1, etc. it can.
- Krill oil can be obtained, for example, by extracting with a suitable organic solvent from a solid content as a raw material derived from krill.
- Suitable organic solvents include, for example, alcohols such as methanol, ethanol, propanol, isopropanol, butanol, propylene glycol, butylene glycol, methyl acetate, ethyl acetate, acetone, chloroform, toluene, pentane, hexane, cyclohexane alone or 2 A combination of two or more species, preferably ethanol or a hexane-ethanol mixture. At that time, the mixing ratio of the solvent or the ratio of the raw material to the solvent may be arbitrarily set.
- the solid content as a raw material derived from the above krill can be obtained by, for example, squeezing the whole or part of the krill to obtain a squeezed liquid, and heating the squeezed liquid to separate the solid content from the water-soluble component.
- the whole krill or part thereof may be heated and solidified as it is to obtain a solid content.
- squeezing commonly used equipment can be used, for example, a hydraulic squeezing machine, a screw press, a meat mining machine, a press dehydrator, a centrifuge, or a combination thereof.
- the above-mentioned compressed solution may be heated at 50 ° C. or higher, preferably 70 to 150 ° C., particularly preferably 85 to 110 ° C. under atmospheric pressure, pressurized or reduced pressure.
- the solid content and water-soluble component are separated by this heating, and the solid content is obtained by filtration or centrifugation.
- the krill oil extracted as described above it is preferable to use the krill oil extracted as described above, but it contains krill oil such as a krill pulverized product, krill flakes, dried krill. Things may be used.
- the alcoholic disorder alleviator and the alcohol metabolism promoter contain an effective amount of krill oil.
- the effective amount herein may be an amount effective for alleviating a disorder caused by alcohol intake or promoting alcohol metabolism.
- krill oil is 10 to 5,000 mg / kg per day, The amount is preferably 100 to 2,000 mg / kg so that the rat can ingest.
- the effective amount per day for humans is preferably 1 to 5,000 mg / kg, particularly preferably 10 to 2,000 mg / kg, specifically 1 to 500 mg / kg per day, preferably 1 to Capsules and supplements that can be ingested at 200 mg / kg, more preferably 1 to 100 mg / kg are preferred.
- alcoholic disorder alleviating agent and alcohol metabolism promoter of the present invention are effective even if taken 30 minutes before ingesting alcohol. Therefore, in order to prevent hangover, alcohol is used. Also preferred is a method of use in which 1 to 20000 mg, preferably 100 to 5000 mg is taken before ingestion.
- the present invention provides a method for preventing or improving hangover and hangover, comprising administering an alcoholic disorder alleviator and an alcohol metabolism promoter containing krill oil to an animal such as a human.
- Excessive alcohol consumption causes symptoms such as headache, nausea, mania, dizziness, malaise, and loss of appetite.
- One possible cause is dehydration caused by alcohol. Since the alcoholic disorder alleviating agent and alcoholic metabolism promoter of the present invention have an effect of lowering the blood alcohol concentration, they are suitable for such applications.
- the present invention provides a method for preventing or treating symptoms and diseases caused by an increase in blood glucose level, comprising administering an alcoholic disorder alleviating agent and an alcohol metabolism promoter containing krill oil to an animal such as a human.
- symptoms caused by an increase in blood glucose level include, for example, malaise, dry mouth, polyuria, hunger, weight gain, and the like.
- diseases caused by an increase in blood glucose level include complications caused by arteriosclerosis. Since the alcoholic disorder alleviating agent and alcohol metabolism promoting agent of the present invention have an effect of suppressing an increase in blood glucose level associated with alcohol intake, they are suitable for such applications.
- the present invention provides a method for preventing or treating alcoholic liver injury, comprising administering an alcoholic disorder alleviating agent and an alcohol metabolism promoter containing krill oil to an animal such as a human.
- alcoholic liver disorder refers to a disease caused by excessive intake of alcohol for a long period of time.
- examples of alcoholic liver disorders include chronic hepatitis such as alcoholic fatty liver, alcoholic liver fibrosis, and alcoholic cirrhosis, and acute hepatitis such as alcoholic hepatitis.
- Alcoholic fatty liver is an early stage alcoholic liver disorder. By reducing the lipolytic function by the liver, neutral fat accumulates in the liver and fatty liver is formed. Alcoholic liver fibrosis refers to an alcoholic fatty liver that has become severe. Hepatocyte necrosis and fibrosis of the surrounding tissue of the necrotic part occur. Alcoholic cirrhosis means that alcoholic liver fibrosis has become severe. Chronic hepatitis progresses, severe hepatocyte destruction occurs, and the entire liver is covered with fibers. In alcoholic hepatitis, hepatocytes are severely damaged.
- Alcoholic liver damage as described above is caused by hepatocyte damage caused by alcohol. Since the alcoholic disorder alleviating agent and alcohol metabolism promoting agent of the present invention can protect hepatocytes and suppress their damage, they are suitable for such applications.
- Blood ethanol concentration Changes in alcohol concentration remaining in the body after alcohol intake can be grasped. When alcohol metabolism is promoted, the blood ethanol concentration decreases and recovers to the normal concentration sooner.
- the blood ethanol concentration can be measured by an ultraviolet absorbance measurement method using F-kit ethanol (JK International).
- Hematocrit value indicates the proportion of blood cells in the whole blood.
- HCT Hematocrit value
- the hematocrit value indicates the volume ratio of blood cells in the blood, and an increase in this value indicates that the water ratio in the blood decreases.
- HCT can be used as an indicator of dehydration associated with alcohol consumption. When alcohol metabolism is promoted, dehydration is resolved, and HCT decreases. HCT can be measured by a sheath flow DC detection method using a multi-item automatic blood cell analyzer (XT-2000i, Sysmex Corporation).
- AST Aspartate aminotransferase activity in blood: AST catalyzes the reaction of producing glutamate and oxaloacetate from aspartate and 2-oxoglutarate. AST is present in hepatocytes, erythrocytes, heart muscle, skeletal muscle, and the like, and flows out into the blood due to cell necrosis. Therefore, the degree of liver damage induced by alcohol intake can be evaluated by measuring the AST activity in blood. The AST activity can be measured by the JSCC standardization method using an automatic analyzer (model 7170, Hitachi, Ltd.). *
- ALT Blood alanine aminotransferase activity: ALT catalyzes the reaction of converting pyruvate and glutamate into alanine and ⁇ -ketoglutarate. ALT exists mainly in the liver, and flows into the blood due to necrosis of hepatocytes. Therefore, the degree of liver damage induced by alcohol intake can be evaluated by measuring the ALT activity in blood. The ALT activity can be measured by the JSCC standardization method using an automatic analyzer (model 7170, Hitachi, Ltd.).
- Acetaldehyde concentration in exhaled breath Acetaldehyde is a causative substance of discomfort induced by alcohol intake and alcoholic liver damage.
- the acetaldehyde concentration in exhaled breath has a corresponding relationship with the blood acetaldehyde concentration. Therefore, a change in blood acetaldehyde concentration can be grasped by measuring the acetaldehyde concentration in exhaled breath.
- the concentration of acetaldehyde contained in exhaled breath should be measured by passing the breath for about 2 minutes through an acetaldehyde detector tube (Gastech Inc., No. 92L) connected to a detector (Gastech Inc., GV-100S). Can do.
- the scale is read from the length of the discolored layer in which the detector tube has changed from yellow to brown, and the reading of the acetaldehyde concentration is corrected by the influence of temperature to obtain a measured value.
- krill oil The components of krill oil can be analyzed as follows. Unless stated otherwise, the analytical values presented herein are based on the methods presented herein.
- the phospholipid content is measured by, for example, dissolving 300 mg of krill oil in hexane and subjecting it to silica gel chromatography, collecting and eluting the adsorbed fraction with chloroform, and measuring the weight of the residue after the solvent is distilled off under reduced pressure. Can be done.
- examples of the antioxidant include dry yeast, glutathione, lipoic acid, quercetin, catechin, coenzyme Q10, enzodinol, proanthocyanidins, anthocyanidins, anthocyanins, carotenes, lycopene, flavonoids, resaveratrol, isoflavones, Examples include zinc, melatonin, ginkgo biloba, moon peach leaf, hibiscus, or extracts thereof.
- vitamins include vitamin A groups (e.g., retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene, and salts thereof), vitamin B groups (e.g., thiamine, thiamine disulfide, dicetiamine, octothiamine, chicotiamine, Bisbutiamine, bisbentiamine, prosultiamine, benfotiamine, fursultiamine, riboflavin, flavin adenine dinucleotide, pyridoxine, pyridoxal, hydroxocobalamin, cyanocobalamin, methylcobalamin, deoxyadenocobalamin, folic acid, tetrahydrofolic acid, dihydrofolic acid , Nicotinic acid, nicotinic amide, nicotinic alcohol, pantothenic acid, panthenol, biotin, choline, inositol,
- the alcoholic disorder alleviating agent and alcohol metabolism promoter of the present invention are in a form suitable for pharmaceutical compositions, functional foods, health foods, supplements, etc., such as granules (including dry syrup), capsules (soft capsules, hard capsules, Capsules), tablets (including chewables), powders (powder), pills and other solid preparations, or liquid preparations such as liquids for internal use (including liquids, suspensions and syrups) It may be prepared in the form.
- additives for formulation for example, excipients, lubricants, binders, disintegrants, fluidizers, dispersants, wetting agents, preservatives, thickeners, pH adjusters, colorants, Examples include flavoring agents, surfactants, and solubilizing agents.
- thickeners such as pectin, xanthan gum, and guar gum, can be mix
- thickeners such as pectin, xanthan gum, and guar gum
- it can also be set as a coating tablet using a coating agent, or it can also be set as a paste-form glue. Furthermore, even if it is a case where it prepares in another form, what is necessary is just to follow the conventional method.
- composition of the present invention may be added to any food or drink as long as it is a food to which oils and fats can be added.
- it can be used as various foods such as beverages, confectionery, breads and soups, or additives thereof.
- the method for producing these foods and drinks is not particularly limited as long as the effects of the present invention are not impaired, and may follow the methods used by those skilled in the art for each application.
- Example 1 Production of krill oil Krill oil can be produced, for example, by any of the methods described in WO2010 / 03749A1 and WO2010 / 03750A1. Specific examples of production are shown below.
- the pressing liquid (3t) was obtained by pressing the Antarctic krill (10t) immediately after catching using a meat mining machine (Bader company make, model BAADER605).
- This compressed liquid (800 kg) was stored in a stainless steel tank and heated by directly administering 140 ° C. water vapor. After confirming that the temperature of the pressing liquid reached 85 ° C. by heating for about 60 minutes, heating was stopped.
- the valve at the bottom of the tank was opened, the liquid component passing through the mesh of 2 mm was removed by natural dropping, and the solid content (thermally coagulated material) on the mesh was washed by showering with the same amount of water (3 t). Thereafter, 12 kg each was stored in an aluminum tray and quickly frozen by a contact freezer.
- the above-mentioned frozen heat-coagulated product (1 t) was put into water (3,000 L), heated with stirring and heated to 65 ° C., and held for 10 minutes. Water was drained using 24 mesh nylon, and the solid content was poured into water (3,000 L, 20 ° C.). After stirring for 15 minutes, drain with 24 mesh nylon, and further treat with a centrifugal dehydrator (Tanabe Centrifuge O-30) for 15 seconds to obtain a solid content (564 kg, moisture 73%). Obtained. Tocopherol (1.54 kg) was added to this solid content, mixed well with a mixer, and dried at a hot air temperature of 60 ° C. for 3.2 hours to obtain a dried product (148.4 kg).
- Extract C Extraction Soot c (390 kg) (105 ° C., loss on drying for 4 hours was 61.8%). Extracts A, B, and C were combined (2,089 kg), concentrated under reduced pressure at a liquid temperature of 60 ° C. or lower, and ethanol and water were distilled off to obtain an extract (141.6 kg). This extract was used as krill oil for the following studies.
- Tables 1 and 2 show the results of analyzing the phospholipid content, astaxanthin content, and fatty acid composition of krill oil.
- Example 2 Administration of krill oil to experimental animals (1) Preparation of test substance Orally administered krill oil was prepared as follows and stored in a brown glass bottle until use. The control group received only the same amount of olive oil. For administration of 200 mg of krill oil: Krill oil was suspended in olive oil using a pestle and mortar, and prepared to contain 200 mg of krill oil in 3 mL of the suspension. For administration of 1,000 mg of krill oil: Krill oil was suspended in olive oil using a pestle and mortar, and 1,000 mg of krill oil was contained in 3 mL of the suspension.
- test substance administered to rats according to the schedule shown in FIG. Unless otherwise stated, rats were housed under the following conditions: Temperature: 20-26 ° C; Relative humidity: 40-70%; Ventilation frequency: 10-20 times / hour; Lighting time: 12 hours (from 7:00 to 19:00); Feed: Free intake of powdered fish meal feed (FR-1, Funabashi Farm Co., Ltd.); Drinking water: Water is freely taken from water bottles.
- breaths were collected from subjects for 30, 60, 90, 120, and 150 minutes.
- the breath was collected by inhaling through the nose and holding it for 10 seconds, and then blowing in so that the chuck-type plastic bag (280 ⁇ 200 ⁇ 0.04 mm) was filled.
- the collected exhaled breath was subjected to ethanol concentration measurement using an ethanol detector tube (Gastech, No. 112L) connected to a detector (Gastech, GV-100S).
- Acetaldehyde was only detected in exhaled breath collected from one of the subjects (5).
- the exhaled breath collected from the other 4 subjects was below the measurement limit.
- FIG. 9 shows changes with time in the concentration of acetaldehyde in exhaled breath collected from one subject. It was shown that the concentration of acetaldehyde in the breath was significantly lower when krill oil was ingested than when olive oil was ingested. Moreover, when krill oil was ingested, the acetaldehyde concentration in the exhalation became below the measurement limit 120 minutes after the start of alcohol ingestion.
- Example 4 Comparison with soybean lecithin and refined fish oil In a subject who selected acetaldehyde in exhaled breath as an index for easily confirming the difference and detected acetaldehyde in exhaled in Example 3, the effects of soybean lecithin and purified fish oil Compared.
- test food Commercially available refined fish oil (28% by weight of EPA, 12% by weight of DHA) and soybean lecithin (60% by weight of phospholipid) were used as other oils.
- Soft capsules containing 250 mg of purified fish oil or soybean lecithin were prepared in the same manner as in Example 3.
- Test method Purified fish oil and soy lecithin soft capsules were ingested by the subject in the same manner as in Example 3, and exhaled breath was collected from the subject and subjected to acetaldehyde concentration measurement.
- FIG. 10 shows the change with time in the concentration of acetaldehyde in the breath together with the results of FIG. It was shown that the acetaldehyde concentration in the breath was significantly lower when krill oil was ingested than when olive oil, purified fish oil, and soy lecithin were ingested.
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Abstract
Description
(1)オキアミ油を有効成分として含有するアルコール性障害緩和剤。
(2)アルコール性障害の緩和が、血中エタノール濃度の上昇の抑制、酒酔い状態の症状の軽減、酒酔い状態の症状の回復促進、肝障害の抑制、脱水症状の抑制、又は血糖値上昇の抑制のいずれかである、(1)に記載のアルコール性障害緩和剤。
(3)アルコール性障害の緩和がオキアミ油によるアルコール吸収抑制及び/又はアルコール代謝促進に基づくものである、(1)又は(2)に記載のアルコール性障害緩和剤。
(4)オキアミ油が、リン脂質を25重量%以上で含有することを特徴とする(1)ないし(3)いずれかに記載のアルコール性障害緩和剤。
(5)オキアミ油の全脂肪酸の5重量%以上がω3高度不飽和脂肪酸である(1)ないし(4)いずれかに記載のアルコール性障害緩和剤。
(6)オキアミ油の全脂肪酸の2重量%以上がエイコサペンタエン酸である(1)ないし(5)いずれかに記載のアルコール性障害緩和剤。
(7)オキアミ油の全脂肪酸の1重量%以上がドコサヘキサエン酸である(1)ないし(6)いずれかに記載のアルコール性障害緩和剤。
(8)オキアミ油の1日あたりの摂取量が1~20000mgである(1)ないし(7)いずれかに記載のアルコール性障害緩和剤。
(9)(1)ないし(8)いずれかに記載のアルコール性障害緩和剤を摂取させるための飲食品。
(10)オキアミ油を1回あたり、1~20000mg摂取させるための(9)に記載の飲食品。 The present invention provides the following alcoholic disorder alleviating agent and food and drink containing the same.
(1) An alcoholic disorder alleviator containing krill oil as an active ingredient.
(2) Alleviation of alcoholic disorder is suppression of increase in blood ethanol concentration, reduction of symptoms of drunk state, promotion of recovery of symptoms of drunk state, suppression of liver injury, suppression of dehydration symptoms, or increase of blood sugar level The alcoholic disorder alleviating agent according to (1), wherein
(3) The alcoholic disorder alleviating agent according to (1) or (2), wherein the alleviation of alcoholic disorder is based on suppression of alcohol absorption by krill oil and / or promotion of alcohol metabolism.
(4) The alcoholic disorder alleviating agent according to any one of (1) to (3), wherein the krill oil contains phospholipid at 25% by weight or more.
(5) The alcoholic disorder alleviating agent according to any one of (1) to (4), wherein 5% by weight or more of all fatty acids in krill oil is ω3 highly unsaturated fatty acid.
(6) The alcoholic disorder alleviating agent according to any one of (1) to (5), wherein 2% by weight or more of all fatty acids in krill oil is eicosapentaenoic acid.
(7) The alcoholic disorder alleviating agent according to any one of (1) to (6), wherein 1% by weight or more of all fatty acids in krill oil is docosahexaenoic acid.
(8) The alcoholic disorder alleviating agent according to any one of (1) to (7), wherein the daily intake of krill oil is 1 to 20000 mg.
(9) A food or drink for ingesting the alcoholic disorder alleviating agent according to any one of (1) to (8).
(10) The food or drink according to (9) for ingesting 1 to 20000 mg of krill oil per time.
(11)オキアミ油を含有するアルコール代謝促進剤。
(12)オキアミ油がオキアミ由来の原料から有機溶媒によって抽出される、(11)に記載のアルコール代謝促進剤。
(13)オキアミ油がオキアミ由来の原料からエタノールによって抽出される、(11)又は(12)に記載のアルコール代謝促進剤。
(14)オキアミ油がリン脂質を25重量%以上で含有する、(11)~(13)のいずれかに記載のアルコール代謝促進剤。
(15)オキアミ油において、ω3高度不飽和脂肪酸が全脂肪酸の5重量%以上を占める、(11)~(14)のいずれかに記載のアルコール代謝促進剤。
(16)オキアミ油がアスタキサンチンを100ppm以上で含有する、(11)~(15)のいずれかに記載のアルコール代謝促進剤。 As another aspect, the present invention provides (11) to (16) an alcohol metabolism promoter, although not limited thereto.
(11) An alcohol metabolism promoter containing krill oil.
(12) The alcohol metabolism promoter according to (11), wherein krill oil is extracted from a krill-derived raw material with an organic solvent.
(13) The alcohol metabolism promoter according to (11) or (12), wherein krill oil is extracted from ethanol from a krill-derived raw material.
(14) The alcohol metabolism promoter according to any one of (11) to (13), wherein the krill oil contains phospholipid at 25% by weight or more.
(15) The alcohol metabolism promoter according to any one of (11) to (14), wherein the ω3 highly unsaturated fatty acid in krill oil accounts for 5% by weight or more of the total fatty acid.
(16) The alcohol metabolism promoter according to any one of (11) to (15), wherein the krill oil contains astaxanthin at 100 ppm or more.
オキアミ油を含有するアルコール代謝促進剤を投与することを含む、アルコール代謝の促進法。
オキアミ油を含有するアルコール代謝促進剤を投与することを含む、アルコール性肝障害、脱水症状に伴う組織障害、又は血糖値の上昇に起因する疾患を予防又は改善する方法。 Furthermore, the present invention provides the following method.
A method for promoting alcohol metabolism, comprising administering an alcohol metabolism promoter containing krill oil.
A method for preventing or ameliorating a disease caused by alcoholic liver disorder, tissue disorder associated with dehydration, or an increase in blood glucose level, comprising administering an alcohol metabolism promoter containing krill oil.
0点: 体姿勢、運動性、正向反射が正常である;
1点: 四肢のバランスは取れないが歩行は可能であり、正向反射は正常である(ほろ酔い状態);
2点: 四肢のバランスが取れず歩行が困難であるが、正向反射は正常である(酩酊、傾眠状態);
3点: 四肢のバランスが取れず歩行が困難であり、正向反射も消失している(泥酔、昏睡状態)。 (2) Observation of general state: The state of drunkness caused by alcohol administration is quantified by observing body posture, mobility and direct reflex. When alcohol metabolism is promoted, the degree of drunkenness is alleviated and recovery to the normal state is accelerated. General status can be assessed by the following criteria:
0 points: normal body posture, mobility and normal reflex;
1 point: The limbs are not balanced, but walking is possible, and the normal reflex is normal (tipy state);
2 points: The limbs are not balanced and walking is difficult, but the normal reflex is normal (酩酊, somnolence);
3 points: The limbs are not balanced and walking is difficult, and the direct reflex is also lost (drunk, coma).
機器:6890NネットワークGCシステム(アジレント・テクノロジー社);
カラム:DB-WAX(カラム長30m、内径250μm、肉厚0.27μm、型番:122-7032、J&W Scientific社);
カラム温度:180から30℃/分の速度で230℃に昇温後、230℃で15分維持;
注入口温度:250℃;
検出器温度:250℃;
検出器:FID;
キャリアーガス:ヘリウム。 Analysis of the fatty acid composition can be performed by subjecting the constituent fatty acid to methyl esterification in boron trifluoride and then subjecting it to gas chromatography. The ratio of the peak area derived from each constituent fatty acid to the total peak area derived from all fatty acids can be calculated to represent the fatty acid composition. The analysis conditions of gas chromatography can be set as follows, for example.
Equipment: 6890N network GC system (Agilent Technology);
Column: DB-WAX (column length 30 m, inner diameter 250 μm, wall thickness 0.27 μm, model number: 122-7032, J & W Scientific);
Column temperature: after being heated to 230 ° C. at a rate of 180 to 30 ° C./min, maintained at 230 ° C. for 15 minutes
Inlet temperature: 250 ° C;
Detector temperature: 250 ° C .;
Detector: FID;
Carrier gas: helium.
オキアミ油は、例えば、WO2010/03749A1やWO2010/03750A1に記載のいずれの方法によっても製造することができる。製造の具体例を以下に示す。 [Example 1] Production of krill oil Krill oil can be produced, for example, by any of the methods described in WO2010 / 03749A1 and WO2010 / 03750A1. Specific examples of production are shown below.
(1)被験物質の調製
経口投与するオキアミ油は、以下のように調製し、使用するまで褐色のガラス瓶中で保存した。対照群は、同量のオリーブ油のみを投与した。
オキアミ油200mg投与用:乳棒及び乳鉢を用いてオキアミ油をオリーブ油に懸濁し、懸濁液3mL中にオキアミ油が200mg含まれるように調製した。
オキアミ油1,000mg投与用:乳棒及び乳鉢を用いてオキアミ油をオリーブ油に懸濁し、懸濁液3mL中にオキアミ油が1,000mg含まれるように調製した。 [Example 2] Administration of krill oil to experimental animals (1) Preparation of test substance Orally administered krill oil was prepared as follows and stored in a brown glass bottle until use. The control group received only the same amount of olive oil.
For administration of 200 mg of krill oil: Krill oil was suspended in olive oil using a pestle and mortar, and prepared to contain 200 mg of krill oil in 3 mL of the suspension.
For administration of 1,000 mg of krill oil: Krill oil was suspended in olive oil using a pestle and mortar, and 1,000 mg of krill oil was contained in 3 mL of the suspension.
エタノール(純度99.5%、和光純薬工業株式会社)と注射用水(株式会社大塚製薬工場)を60.3:39.7の割合で混合することによって調製し、褐色のガラス瓶中で使用するまで室温保存した。 (2) Preparation of 60% (v / v) ethanol solution Ethanol (purity 99.5%, Wako Pure Chemical Industries, Ltd.) and water for injection (Otsuka Pharmaceutical Factory Co., Ltd.) at a ratio of 60.3: 39.7 Prepared by mixing and stored at room temperature until used in a brown glass bottle.
図1に示すスケジュールに従って、被験物質及び60%(v/v)エタノール溶液をラットに投与した。特に言及がない限り、ラットは以下に示す条件で飼育した:
温度: 20~26℃;
相対湿度: 40~70%;
換気回数: 10~20回/時間;
照明時間: 12時間(7:00~19:00);
飼料: 魚粉抜き粉末飼料(FR-1、株式会社フナバシファーム)の自由摂取;
飲料水: 上水道水を給水瓶から自由摂取。 (3) Administration of test substance and 60% (v / v) ethanol solution The test substance and 60% (v / v) ethanol solution were administered to rats according to the schedule shown in FIG. Unless otherwise stated, rats were housed under the following conditions:
Temperature: 20-26 ° C;
Relative humidity: 40-70%;
Ventilation frequency: 10-20 times / hour;
Lighting time: 12 hours (from 7:00 to 19:00);
Feed: Free intake of powdered fish meal feed (FR-1, Funabashi Farm Co., Ltd.);
Drinking water: Water is freely taken from water bottles.
60%(v/v)エタノール溶液の投与前、投与後1、2、及び24時間において採取した血液にヘパリンを添加し、血中エタノールの濃度を測定し、投与群ごとの平均値を算出した(図2)。 (4) Measurement of blood ethanol concentration Before administration of 60% (v / v) ethanol solution, heparin was added to blood collected at 1, 2, and 24 hours after administration, and the concentration of blood ethanol was measured. The average value for each administration group was calculated (FIG. 2).
エタノールの投与前、投与後1、2、4、及び24時間におけるラットの一般状態を観察した(図3)。60%(v/v)エタノール溶液を投与しなかった無処理群(A1)を除く全ての投与群(A2~A4)において、エタノール投与1時間後からほろ酔い状態、酩酊、傾眠状態及び泥酔、昏睡状態が観察され、エタノール投与による酒酔いの状態が観察された。その中でオキアミ油1,000mg/kg投与群(A4)においては、オリーブ油投与群と比較して酒酔いの状態が有意に抑制され、その効果は60%(v/v)エタノール溶液の投与後24時間においてより顕著になった。 (5) Observation of general condition of rat General condition of rat was observed before administration of ethanol, 1, 2, 4, and 24 hours after administration (FIG. 3). In all administration groups (A2 to A4) except for the untreated group (A1) that did not receive the 60% (v / v) ethanol solution, the tipsy state, mania, somnolence and drunkness, coma from 1 hour after ethanol administration The condition was observed and the state of drunkness by ethanol administration was observed. Among them, in the krill oil 1,000 mg / kg administration group (A4), the state of drunkness was significantly suppressed as compared with the olive oil administration group, and the effect was after the administration of the 60% (v / v) ethanol solution. It became more prominent at 24 hours.
60%(v/v)エタノール溶液の投与前、投与後4時間、及び24時間において採取した血液にEDTA-2Kを添加し、HCTの測定に用いた(図4)。 (6) Measurement of hematocrit value (HCT) EDTA-2K was added to blood collected at 60 hours (v / v) ethanol solution before administration, 4 hours and 24 hours after administration, and used for HCT measurement ( FIG. 4).
60%(v/v)エタノール溶液の投与前、及び投与後24時間において採取した血液にヘパリンを添加し、1700×g、4℃で15分間遠心分離することによって血漿を得た。この血漿をAST活性の測定に用いた(図5)。 (7) Measurement of blood aspartate aminotransferase (AST) activity Heparin was added to blood collected before and after administration of a 60% (v / v) ethanol solution at 1700 × g at 4 ° C. Plasma was obtained by centrifugation for 15 minutes. This plasma was used for measurement of AST activity (FIG. 5).
60%(v/v)エタノール溶液の投与前、及び投与後24時間において採取した血液にヘパリンを添加し、1700×g、4℃で15分間遠心分離することによって血漿を得た。この血漿をALT活性の測定に用いた(図6)。 (8) Measurement of blood alanine aminotransferase (ALT) activity Heparin was added to blood collected before and after administration of a 60% (v / v) ethanol solution, and 1700 × g at 4 ° C. Plasma was obtained by centrifuging for minutes. This plasma was used for measurement of ALT activity (FIG. 6).
60%(v/v)エタノール溶液の投与前、及び投与後24時間において採取した血液にヘパリンを添加し、1700×g、4℃で15分間遠心分離することによって血漿を得た。この血漿を用いてグルコース濃度の測定を行った(図7)。 (9) Measurement of blood glucose level Plasma was obtained by adding heparin to blood collected before and after administration of a 60% (v / v) ethanol solution and centrifuging at 1700 × g and 4 ° C. for 15 minutes. Got. Using this plasma, the glucose concentration was measured (FIG. 7).
オキアミ油のヒトにおけるアルコール摂取への影響をアルコール摂取後の呼気中のエタノール濃度及び呼気中のアセトアルデヒド濃度を測定することにより検討した。 [Example 3] Effect of krill oil on alcohol intake in humans The effect of krill oil on alcohol intake in humans was examined by measuring the ethanol concentration in exhaled breath and the acetaldehyde concentration in exhaled breath after alcohol intake.
実施例1で調製したオキアミ油又は精製オリーブ油を1粒あたり250mg含有するゼラチンのソフトカプセルを調製した。両ソフトカプセルは着色したものを用い、外観から中身の区別が出来ないようにした。 (1) Preparation of test food Gelatin soft capsules containing 250 mg per grain of krill oil or purified olive oil prepared in Example 1 were prepared. Both soft capsules were colored so that the contents could not be distinguished from the appearance.
40歳以上の健康な男性5名。 (2) Subjects Five healthy men over 40 years old.
オリーブ油を対照とした二重盲検クロスオーバー試験を実施した。ウォッシュアウト期間は2週間とした。 (3) Test method A double-blind crossover test was conducted using olive oil as a control. The washout period was 2 weeks.
エタノールは被験者(5名)から採取した全ての呼気において検出された。呼気中のエタノール濃度の経時変化を図8に示した。図中のエタノール濃度は、被験者(5名)から採取した呼気中のエタノール濃度の平均値を示す。アルコール摂取開始後30分の呼気においてエタノール濃度が最も高くなったが、オキアミ油を摂取した場合とオリーブ油を摂取した場合のエタノール濃度の相違に有意差は認められなかった。しかし、アルコール摂取開始後60分の呼気において、オキアミ油を摂取した場合にはオリーブ油を摂取した場合に比べて有意(P=0.04、Wilcoxon signed rank test)にエタノール濃度が減少していることが示された。 (4) Results Ethanol was detected in all exhaled breaths collected from the subjects (5 subjects). The time course of the ethanol concentration in exhaled breath is shown in FIG. The ethanol concentration in the figure shows the average value of the ethanol concentration in exhaled breath collected from subjects (5 subjects). The ethanol concentration was highest at 30 minutes after the start of alcohol intake, but no significant difference was observed in the difference in ethanol concentration between ingestion of krill oil and ingestion of olive oil. However, at 60 minutes after the start of alcohol intake, it was shown that the ethanol concentration was significantly decreased (P = 0.04, Wilcoxon signed rank test) when taking krill oil compared to taking olive oil. It was done.
差を確認しやすい指標として呼気中のアセトアルデヒドを選択し、実施例3で呼気中にアセトアルデヒドを検出した被験者において、大豆レシチン、精製魚油による効果と比較した。 [Example 4] Comparison with soybean lecithin and refined fish oil In a subject who selected acetaldehyde in exhaled breath as an index for easily confirming the difference and detected acetaldehyde in exhaled in Example 3, the effects of soybean lecithin and purified fish oil Compared.
他の油として市販の精製魚油(総脂肪酸中、EPA 28重量%、DHA 12重量%)及び大豆レシチン(リン脂質60重量%)を使用した。実施例3と同様に精製魚油又は大豆レシチンを250mg含有するソフトカプセルを調製した。 (1) Preparation of test food Commercially available refined fish oil (28% by weight of EPA, 12% by weight of DHA) and soybean lecithin (60% by weight of phospholipid) were used as other oils. Soft capsules containing 250 mg of purified fish oil or soybean lecithin were prepared in the same manner as in Example 3.
実施例3で呼気中にアセトアルデヒドが検出された50歳の健康な男性(体重65kg)。 (2) Subject A 50-year-old healthy man (body weight 65 kg) in which acetaldehyde was detected in exhaled breath in Example 3.
実施例3と同様の方法で精製魚油、及び大豆レシチンのソフトカプセルを被験者に摂取させ、被験者から呼気を採取し、アセトアルデヒド濃度の測定に供した。 (3) Test method Purified fish oil and soy lecithin soft capsules were ingested by the subject in the same manner as in Example 3, and exhaled breath was collected from the subject and subjected to acetaldehyde concentration measurement.
呼気中のアセトアルデヒド濃度の経時変化を図9の結果と合わせて、図10に示した。オキアミ油を摂取した場合、オリーブ油、精製魚油、及び大豆レシチンを摂取した場合に比べて、呼気中のアセトアルデヒド濃度が著しく低いことが示された。 (4) Results FIG. 10 shows the change with time in the concentration of acetaldehyde in the breath together with the results of FIG. It was shown that the acetaldehyde concentration in the breath was significantly lower when krill oil was ingested than when olive oil, purified fish oil, and soy lecithin were ingested.
Claims (10)
- オキアミ油を有効成分として含有するアルコール性障害緩和剤。 An alcoholic disorder alleviator containing krill oil as an active ingredient.
- アルコール性障害の緩和が、血中エタノール濃度の上昇の抑制、酒酔い状態の症状の軽減、酒酔い状態の症状の回復促進、肝障害の抑制、脱水症状の抑制、又は血糖値上昇の抑制のいずれかである、請求項1に記載のアルコール性障害緩和剤。。 Alleviation of alcoholic disorder can suppress the increase in blood ethanol concentration, reduce symptoms of drunk state, promote recovery of symptoms of drunk state, suppress liver damage, suppress dehydration, or suppress increase in blood glucose level The alcoholic disorder alleviating agent according to claim 1, which is any one of them. .
- アルコール性障害の緩和がオキアミ油によるアルコール吸収抑制及び/又はアルコール代謝促進に基づくものである、請求項1又は2に記載のアルコール性障害緩和剤。 The alcoholic disorder alleviating agent according to claim 1 or 2, wherein the alleviation of alcoholic disorder is based on suppression of alcohol absorption by krill oil and / or promotion of alcohol metabolism.
- オキアミ油が、リン脂質を25重量%以上で含有することを特徴とする請求項1ないし3いずれか1項に記載のアルコール性障害緩和剤。 4. The alcoholic disorder alleviating agent according to any one of claims 1 to 3, wherein the krill oil contains phospholipid in an amount of 25% by weight or more.
- オキアミ油の全脂肪酸の5重量%以上がω3高度不飽和脂肪酸である請求項1ないし4いずれか1項に記載のアルコール性障害緩和剤。 The alcoholic disorder alleviating agent according to any one of claims 1 to 4, wherein 5% by weight or more of all fatty acids in krill oil is ω3 highly unsaturated fatty acid.
- オキアミ油の全脂肪酸の2重量%以上がエイコサペンタエン酸である請求項1ないし5いずれか1項に記載のアルコール性障害緩和剤。 The alcoholic disorder alleviating agent according to any one of claims 1 to 5, wherein 2% by weight or more of all fatty acids of krill oil is eicosapentaenoic acid.
- オキアミ油の全脂肪酸の1重量%以上がドコサヘキサエン酸である請求項1ないし6いずれか1項に記載のアルコール性障害緩和剤。 The alcoholic disorder alleviating agent according to any one of claims 1 to 6, wherein 1% by weight or more of all fatty acids in krill oil is docosahexaenoic acid.
- オキアミ油の1日あたりの摂取量が1~20000mgである請求項1ないし7いずれか1項に記載のアルコール性障害緩和剤。 The alcoholic disorder alleviator according to any one of claims 1 to 7, wherein the daily intake of krill oil is 1 to 20000 mg.
- 請求項1ないし8いずれか1項に記載のアルコール性障害緩和剤を摂取させるための飲食品。 Food or drink for ingesting the alcoholic disorder alleviating agent according to any one of claims 1 to 8.
- オキアミ油を1回あたり、1~20000mg摂取させるための請求項9に記載の飲食品。 10. The food or drink according to claim 9 for ingesting 1 to 20000 mg of krill oil once.
Priority Applications (4)
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CN201180042380.XA CN103096904B (en) | 2010-09-01 | 2011-09-01 | Alcoholic injury alleviant |
JP2012531956A JP5271454B2 (en) | 2010-09-01 | 2011-09-01 | Alcoholic disorder alleviator |
US13/820,170 US8691297B2 (en) | 2010-09-01 | 2011-09-01 | Alcoholic injury mitigating agent |
US14/148,053 US9061035B2 (en) | 2010-09-01 | 2014-01-06 | Alcoholic injury mitigating agent |
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US13/820,170 A-371-Of-International US8691297B2 (en) | 2010-09-01 | 2011-09-01 | Alcoholic injury mitigating agent |
US14/148,053 Continuation US9061035B2 (en) | 2010-09-01 | 2014-01-06 | Alcoholic injury mitigating agent |
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JP2015048339A (en) * | 2013-09-03 | 2015-03-16 | 雪印メグミルク株式会社 | Alcohol metabolism promoting agent |
JP2017006011A (en) * | 2015-06-17 | 2017-01-12 | 京華堂實業股▲ふん▼有限公司 | Alcoholic beverage composition having effect of shortening drunkenness time |
JP2018048118A (en) * | 2016-08-29 | 2018-03-29 | 大連槿蔵商貿有限公司Dalian JinZang Commercial and Trading Co., Ltd. | Application of conjugated linoleic acid or derivative thereof in the preparation of aldehyde dehydrogenase promoter |
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EP2570126B1 (en) * | 2011-09-16 | 2014-03-26 | Darius Rassoulian | Use of melatonin for treating acute alcohol intoxication |
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CN111920052A (en) * | 2019-05-13 | 2020-11-13 | 安琪酵母股份有限公司 | Composition with functions of dispelling effects of alcohol and protecting liver and preparation method and application thereof |
CN112535716B (en) * | 2019-09-20 | 2022-04-15 | 江阴持一堂医药科技有限公司 | Granules for treating alcoholic liver injury and preparation method and application thereof |
US20230210802A1 (en) * | 2022-01-05 | 2023-07-06 | Zefit Inc. | Composition for relieving hangover and improving liver function |
CN117814318A (en) * | 2024-01-18 | 2024-04-05 | 逢时(青岛)海洋科技有限公司 | Liver-protecting compound composition, preparation method and application thereof |
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Cited By (3)
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JP2015048339A (en) * | 2013-09-03 | 2015-03-16 | 雪印メグミルク株式会社 | Alcohol metabolism promoting agent |
JP2017006011A (en) * | 2015-06-17 | 2017-01-12 | 京華堂實業股▲ふん▼有限公司 | Alcoholic beverage composition having effect of shortening drunkenness time |
JP2018048118A (en) * | 2016-08-29 | 2018-03-29 | 大連槿蔵商貿有限公司Dalian JinZang Commercial and Trading Co., Ltd. | Application of conjugated linoleic acid or derivative thereof in the preparation of aldehyde dehydrogenase promoter |
Also Published As
Publication number | Publication date |
---|---|
US9061035B2 (en) | 2015-06-23 |
CN103096904A (en) | 2013-05-08 |
US8691297B2 (en) | 2014-04-08 |
JPWO2012029898A1 (en) | 2013-10-31 |
CN103096904B (en) | 2016-03-09 |
US20140120172A1 (en) | 2014-05-01 |
JP5271454B2 (en) | 2013-08-21 |
US20130156861A1 (en) | 2013-06-20 |
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